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Although immune checkpoint inhibition (ICI)-based approaches have shown promising activity in early-phase studies, the optimal therapeutic combinations and the feasibility of non-operative management (NOM) in resectable disease remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This exploratory, retrospective, multicenter, real-world study included 55 patients with resectable dMMR\/MSI-H GEA, who were divided into subgroups, characterized and compared according to treatment strategy (chemotherapy, chemoimmunotherapy, immunotherapy and initial resection). Pathological and clinical complete response (pCR, cCR), progression-free (PFS) and overall survival (OS) were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients received chemotherapy (n=10), chemoimmunotherapy (n=16), immunotherapy (n=13), or initial resection without subsequent systemic treatment (n=16). Forty five (82%) patients had surgical resection. The pCR rate was 22% (n=2\/9) in the chemotherapy, 27% (n=4\/15) in the chemoimmunotherapy, and 100% (n=5\/5) in the immunotherapy (i.e., doublet ICI) subgroup, respectively. The overall cCR rate in NOM patients was 33% (n=3\/9), with rates of 37.5% (n=3\/8) in the immunotherapy subgroup and 0% (n=0\/1) in the chemoimmunotherapy subgroup. Complete response rates (pCR\/cCR) were significantly associated with PD-L1 CPS \u226510 (p=0.027).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This real-world study is, to our knowledge, the first to evaluate a broad spectrum of therapeutic combinations in patients with resectable MSI-H\/dMMR GEA, showing meaningful antitumor activity, particularly with doublet ICI. Given the challenges of conducting randomized prospective trials in this setting, such real world data may support clinicians in guiding therapeutic decision-making.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10120-026-01776-1","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:29:58Z","timestamp":1784780998000},"page":"949-959","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic management of resectable mismatch-repair deficient\/microsatellite instability-high gastroesophageal adenocarcinoma: a real-world analysis from Austria"],"prefix":"10.1007","volume":"29","author":[{"given":"Martin","family":"Korpan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Nothdurfter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Doleschal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Roider-Schur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leopold","family":"\u00d6hler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewald","family":"W\u00f6ll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth S.","family":"Bergen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald W.","family":"Prager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrang","family":"Mozayani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S.","family":"Berghoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Preusser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Puhr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Huemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-0873","authenticated-orcid":false,"given":"Ayseg\u00fcl","family":"Ilhan-Mutlu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"1776_CR1","first-page":"229","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, et al. 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EW received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Amgen, Astella Pharma, Astra Zeneca, BMS, Celgen, Daiichi Sankyo, Ebewe, Eisai, Eli Lilly, Elsevier, Gilead, GSK, Janssen Cilag, Johnson&Johnson, Jazz Pharma, Merck, MSD, Novartis, Pierre Fabre, Pfizer, Ratiopharm, Roche, Sanofi Aventis, Servier, Stemline, Takeda; L\u00d6 received honoraria or advisory role fees from Amgen, Astra Zeneca, BMS, Daiichi Sankyo, Eisai, Gilead, GSK, Janssen Cilag, Johnson&Johnson, Merck, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi Aventis, Servier; JMB received travel support from Amgen via institutional nomination and honoraria for lectures, consultation or advisory board participation from MSD; ESB received travel support from Daiichi Sankyo and Jazz Pharmaceuticals via institutional nomination and honoraria for lectures, consultation or advisory board participation from Servier and Merck.; GWP has to declare: advisory board meetings\/symposia fees: Merck Serono, BMS, Roche, Amgen, Sanofi, Lilly, Servier, Taiho, Bayer, Halozyme, MSD, Celgene, Pierre Fabre, Incyte, Arcus, Revolution Medicines, Abbvie, Takeda, JazzPharma.; ASB has research support from Daiichi Sankyo, Roche and honoraria for lectures, consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo, AstraZeneca, CeCaVa, Seagen, Alexion, Servier, Pfizer, Ygion as well as travel support from Roche, Gilead, Amgen and AbbVie.; MP received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, Janssen, Servier, Miltenyi, B\u00f6hringer-Ingelheim, Telix, Medscape, OncLive, Medac, Nerviano Medical Sciences, ITM Oncologics GmbH, AdAcAp, Crinetics.; HCP received travel support from Eli Lilly, MSD, Novartis, Pfizer, PharmaMar and Roche and received lecture honoraria from Eli Lilly.; FH received honoraria from Lilly, Pierre Fabre, Amgen, Servier, Daiichi Sankyo, BMS, Merck, Sanofi, Roche, Janssen, PharmaMar, Astellas, Johnson & Johnson, AstraZeneca, BeOne; and travel support from Servier, BMS, Roche, Merck, Pharmamar, Pfizer, Pierre Fabre, Sanofi, Daiichi Sankyo, Gilead, Jazz Pharmaceuticals.; AIM participated in advisory boards by MSD, Servier, Daiichi Sankyo, BMS, Amgen and Astellas, lecture honoraria from Eli Lilly, Servier, BMS, MSD, Astellas, Astra Zeneca, BeiGene, Amgen, Merck and Daiichi Sankyo, received consulting fees fromm Astellas, MSD, Amgen, Astra Zeneca, BeiGene, and Roche, and travel support (all via institutional nomination) from BMS, Roche, Eli Lilly, Daiichi Sankyo, Jazz and BeiGene.; All other co-authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Due to the retrospective design no explicit informed consent was necessary for this study. This is in accordance with local ethical standards and was approved by the ethics committee of each institution, as stated above.","order":2,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were in accordance with the ethical standards of the responsible committee and with the Helsinki Declaration of 1964 and later versions. The study was approved by the ethics committee of each participating institution: Medical University of Vienna (reference number: 1688\/2025); Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, Salzburg, Austria (reference number: 1132\/2025); Department of Internal Medicine, Krankenhaus St. Vinzenz Zams (reference number 1353\/2025); 1st Department of Internal Medicine \/ Oncology at St. Josef Hospital (reference number: 1047\/2025). The risk of publication of sensitive patient data was minimized by restrictions of data accession and pseudonymized statistical analysis.","order":3,"name":"Ethics","label":"Institutional review board statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Artificial intelligence (AI)-based tools were used to support specific components of this study. ChatGPT (OpenAI, GPT-5) was utilized to assist with R programming for statistical analyses, data visualization, and figure generation. All aspects of conceptualization, study design, data interpretation, and critical reasoning were performed by the authors. All AI-assisted outputs were thoroughly reviewed, verified, and edited by the authors, who take full responsibility for the accuracy and integrity of the final manuscript.","order":4,"name":"Ethics","label":"Statement on the use of artificial intelligence","group":{"name":"EthicsHeading","label":"Declarations"}}]}}